Thermoresponsive Polymer Nanoparticles From Epoxidized Oleyl Methacrylate: Synthesis, Characterization, and In Vitro Evaluation

ABSTRACT Thermoresponsive polymer nanoparticles (PNPs) were developed from epoxidized oleyl methacrylate (EOM), an olive oil–derived renewable monomer bearing reactive epoxide groups that enable post‐ or pre‐polymerization functionalization for future drug, imaging, or targeting molecule conjugation. Neutral and cationic PNPs were synthesized by UV‐initiated free‐radical polymerization of N‐isopropylacrylamide (NIPAM), EOM, and 2‐aminoethyl methacrylamide (2‐AEMA) introduced to generate cationic surface chemistry. Dynamic light scattering showed hydrodynamic diameters of 188.2 nm (neutral; PDI 0.079) and 222.4 nm (cationic; PDI 0.200), while cationic PNPs exhibited a high positive zeta potential (+38.6 ± 5.04 mV). Thermoresponsive behavior assessed by DLS revealed a sharp LCST‐type transition for neutral PNPs at ~28°C–32°C, whereas cationic PNPs displayed a broader, shifted transition at ~35°C–42°C (~38°C), consistent with enhanced polymer–water interactions. In vitro, cationic PNPs reduced HCT116 colorectal cancer cell viability in a dose‐dependent manner (IC 50 = 0.26 ± 0.02 mg/mL at 24 h) while showing no significant toxicity toward HUVECs. Scratch assays indicated inhibited HCT116 migration at 0.05–0.15 mg/mL. Hemocompatibility testing showed no detectable hemolysis up to 0.3 mg/mL and no effect on coagulation at ≤ 0.1 mg/mL, whereas ≥ 0.15 mg/mL inhibited clot formation. These results support EOM‐based cationic thermoresponsive PNPs as sustainable, modular nanoplatforms for cancer‐oriented biomedical applications.